RIN2 p.Ala519=
c.1557C>T · rs372947881 · VCV695752
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.244%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -15 |
| Overall | ||
| CADD | 0.391 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.244%
African / African-American · 183/75,056 alleles
Filtering AF
0.215%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.204%
Overall
0.0125%
201/1,613,990 alleles · rare
exomes 97/1,461,690 · genomes 104/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.244% | 410 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,166 |
| Admixed American | 0.00333% | 30,009 |
| European (non-Finnish) | 8.48e-05% | 1,179,892 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- RIN2
- Protein
- p.Ala519=
- Coding
- c.1557C>T
- MANE Select
- NM_018993
- dbSNP
- rs372947881
- Type
- single nucleotide variant
- Location
- chr20:19975582 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 64.30
Similar variants
- RIN2 p.Ala519Pro Uncertain significance ★ ⚠ same residue
- RIN2 p.Ala205Val Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala72Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Ala8Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg135Cys Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg170Trp Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg255Thr Uncertain significance ★★ ⚠ same type
- RIN2 p.Arg290Leu Uncertain significance ★★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/rin2-p-ala519 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown